Neuropeptide Y regulates cholesterol uptake and efflux in macrophages and promotes foam cell formation

The dysregulation of lipid metabolic pathways (cholesterol uptake and efflux) in macrophages results in the formation of lipid‐dense macrophages, named foam cells, that participate in plaque formation. NPY binding to NPY receptors in macrophages can modulate cell functions and affect the process of...

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Autores principales: Cai, Yu, Wang, Zhengchao, Li, Lun, He, Li, Wu, Xinying, Zhang, Mingjing, Zhu, Pengfei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9639043/
https://www.ncbi.nlm.nih.gov/pubmed/36172879
http://dx.doi.org/10.1111/jcmm.17561
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author Cai, Yu
Wang, Zhengchao
Li, Lun
He, Li
Wu, Xinying
Zhang, Mingjing
Zhu, Pengfei
author_facet Cai, Yu
Wang, Zhengchao
Li, Lun
He, Li
Wu, Xinying
Zhang, Mingjing
Zhu, Pengfei
author_sort Cai, Yu
collection PubMed
description The dysregulation of lipid metabolic pathways (cholesterol uptake and efflux) in macrophages results in the formation of lipid‐dense macrophages, named foam cells, that participate in plaque formation. NPY binding to NPY receptors in macrophages can modulate cell functions and affect the process of atherosclerotic plaques. The present study aimed to determine whether NPY affects the formation of macrophage‐derived foam cells and its underlying mechanisms in macrophages. THP‐1‐derived macrophages were incubated with oxidized low‐density lipoprotein (ox‐LDL) and treated with different concentrations of NPY. We analysed the relative levels of proteins related to cholesterol uptake and efflux. We found that NPY effectively increased cholesterol uptake and intracellular cholesterol content via the Y1 and Y5 receptors, and this effect was blocked by Y1 and Y5 antagonists. Mechanistically, NPY enhanced the expression of SRA and CD36 via the PKC/PPARγ pathways, promoting macrophage cholesterol uptake. Moreover, NPY significantly decreased cholesterol efflux to the extracellular cholesterol acceptors ApoA1 and HDL in macrophages. NPY mediated decreases in ABCA1, ABCG1 and SR‐BI expression through the inhibition of the JAK/STAT3 pathways. Our results suggest that NPY binding to the Y1 and Y5 receptors enhances foam cell formation by regulating cholesterol uptake and efflux in macrophages.
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spelling pubmed-96390432022-11-14 Neuropeptide Y regulates cholesterol uptake and efflux in macrophages and promotes foam cell formation Cai, Yu Wang, Zhengchao Li, Lun He, Li Wu, Xinying Zhang, Mingjing Zhu, Pengfei J Cell Mol Med Original Articles The dysregulation of lipid metabolic pathways (cholesterol uptake and efflux) in macrophages results in the formation of lipid‐dense macrophages, named foam cells, that participate in plaque formation. NPY binding to NPY receptors in macrophages can modulate cell functions and affect the process of atherosclerotic plaques. The present study aimed to determine whether NPY affects the formation of macrophage‐derived foam cells and its underlying mechanisms in macrophages. THP‐1‐derived macrophages were incubated with oxidized low‐density lipoprotein (ox‐LDL) and treated with different concentrations of NPY. We analysed the relative levels of proteins related to cholesterol uptake and efflux. We found that NPY effectively increased cholesterol uptake and intracellular cholesterol content via the Y1 and Y5 receptors, and this effect was blocked by Y1 and Y5 antagonists. Mechanistically, NPY enhanced the expression of SRA and CD36 via the PKC/PPARγ pathways, promoting macrophage cholesterol uptake. Moreover, NPY significantly decreased cholesterol efflux to the extracellular cholesterol acceptors ApoA1 and HDL in macrophages. NPY mediated decreases in ABCA1, ABCG1 and SR‐BI expression through the inhibition of the JAK/STAT3 pathways. Our results suggest that NPY binding to the Y1 and Y5 receptors enhances foam cell formation by regulating cholesterol uptake and efflux in macrophages. John Wiley and Sons Inc. 2022-09-29 2022-11 /pmc/articles/PMC9639043/ /pubmed/36172879 http://dx.doi.org/10.1111/jcmm.17561 Text en © 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Cai, Yu
Wang, Zhengchao
Li, Lun
He, Li
Wu, Xinying
Zhang, Mingjing
Zhu, Pengfei
Neuropeptide Y regulates cholesterol uptake and efflux in macrophages and promotes foam cell formation
title Neuropeptide Y regulates cholesterol uptake and efflux in macrophages and promotes foam cell formation
title_full Neuropeptide Y regulates cholesterol uptake and efflux in macrophages and promotes foam cell formation
title_fullStr Neuropeptide Y regulates cholesterol uptake and efflux in macrophages and promotes foam cell formation
title_full_unstemmed Neuropeptide Y regulates cholesterol uptake and efflux in macrophages and promotes foam cell formation
title_short Neuropeptide Y regulates cholesterol uptake and efflux in macrophages and promotes foam cell formation
title_sort neuropeptide y regulates cholesterol uptake and efflux in macrophages and promotes foam cell formation
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9639043/
https://www.ncbi.nlm.nih.gov/pubmed/36172879
http://dx.doi.org/10.1111/jcmm.17561
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